Project Summary/Abstract ?Analyses of host-microbiota interactions in aging C. elegans hosts? Gut microbiota ? microorganisms and their genes ? influence host physiology. Microorganisms such as bacteria can affect hosts by causing improved or poor health states. For example, gut bacteria can provide nutrients or protection to the host, but also can be pathogenic and cause poor intestinal function. Intestinal microbial composition is relatively stable during adulthood, but it may begin to be less stable and more variable with age. Recent advances in sequencing technology have allowed us to better understand how manipulation of the types of bacteria, and their genes may lead to healthy aging of the host. However, this work is complicated by the large inter-individual variability in aged subjects, and the complexity of the microbiota within intestines of higher organisms. Thus, this project aims to utilize the model organism C. elegans, a microscopic roundworm, to examine bacterial responses in different hosts. C. elegans allows for genetic control of both the bacteria and the hosts to ascertain bacterial gene expression and metabolism. Specifically, bacteria can form biofilms in response to their host environments, primarily to protect themselves from external stresses such as host immune responses. We know that bacteria accumulate in older worms, but less is known about how bacteria form biofilms and whether biofilm formation affects lifespan. Our proposal examines biofilm formation, expression of biofilm-related genes during specific steps of formation, and the effect of blocking biofilms on known models of aging. In C. elegans, models of aging include pathways that act through insulin signaling, caloric intake, and mitochondrial respiration, all of which may generate different host environments which affect bacteria. In addition, we examine a component of the apical membrane of intestines, which interfaces and serves to communicate with bacteria. In particular, we examine a class of enzymes called ceramide glucosyltransferases, which make the complex sphingolipid glucosylceramide. Glucosylceramides have been shown to serve as binding partners for some bacteria and may mediate biofilm formation. Thus, animals lacking or with increased levels of glucosylceramide may alter biofilm formation. We hope that this work on host/microbiome interactions will inform the scientific community on the development of novel treatment strategies to improve healthy aging via host-microbiota interactions.